Bioreactors are systems in which biological activity can be sustained. In some cases, bioreactors can be used to stimulate cell growth, chemical reactions, or other activity. Current bioreactors used for cell culture are in need of improvement in various respects to better recapitulate the in vivo environment. As one example, it is often difficult to generate cell clusters greater than several cells in thickness, in part because adequate transportation of nutrients, particularly oxygen, to cells in a cluster becomes more difficult as the distance between the cluster surface and the cells increases.
In some cases, cell viability has been estimated to decrease from about 60% at the cluster surface to about 5% at a distance of 100 μm from the surface. Cells separated from the surface by such a distance can become hypoxic and die, leading to necrosis of the culture. Thus, to more effectively culture cells, it is desirable that nutrients (e.g., oxygen) be made more readily available to, and wastes (e.g., carbon dioxide) be more quickly removed from, the culture volume.
Tissue growth in a living organism requires propagation of blood vessels surrounded by cellular tissue. In some cases, the cellular tissue grows in tandem with the blood vessels, which provides adequate delivery of nutrients to, and efficient removal of wastes from, the cellular tissue. Attempts to mimic such tissue growth in lab-based bioreactors have not been as successful as some have hoped, and in vitro production of biological tissues remains difficult.
Three dimensional (3D) cell culture techniques can provide advantages over two dimensional (2D) cell culture techniques. For example, in the study of biological processes involved in cancer, monolayer cell culture in a 2D environment may not adequately simulate complex features of tumor growth, such as cell morphology, metabolism, migration, signaling, gene expression, and differentiation. Systems that allow 3D culture of cells, for example cancer cells, are desirable because such systems promote more natural cell growth by allowing interactions both between cells and between cells and the extracellular matrix.
Current 3D culture techniques, including explant cultures, 3D scaffolds, and PEG and collagen hydrogels are currently suboptimal. For example, as cultured tumor cells grow into larger structures (i.e., spheroids or clusters) using current 3D culture techniques, the clusters often develop central hypoxia because oxygen is relatively abundant at the culture's surface and less so at its interior. In contrast, tumors in vivo grow around biological vasculature such that hypoxia increases as the distance of the cells from the vasculature increases.
Hydrogels are highly absorbent hydrophilic polymeric materials. Silicone hydrogel materials are biocompatible and have relatively high oxygen permeability. As a result, silicone hydrogels are sometimes used to make contact lenses that provide increased comfort to users and allow users to wear the lenses in the eyes for longer periods of time without inducing corneal hypoxia, edema, or inflammation.